ABSTRACT

Oral innate immunity is led by neutrophils. It is still unclear how their main antimicrobial mechanisms against different biofilms may contribute to balance or dysregulation in the oral cavity. We investigated the capacity of commensal (Streptococcus oralis) and pathogenic (Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans) monospecies biofilms to induce or to inhibit selected antimicrobial mechanisms of neutrophils. S. oralis induced neutrophil extracellular traps (NETs) formation, reactive oxygen species (ROS) production, and matrix metalloproteinases (MMPs) 8 and 9 secretion. However, these responses were partially reduced in PMA-activated neutrophils indicating a balance-like neutrophil response, which might be important for the maintenance of oral health. P. gingivalis generally induced ROS. Reduced NET formation and significantly decreased MMP secretion were detectable in activated neutrophils highlighting P. gingivalis’ nucleolytic and proteolytic activity, which might support bacterial colonization and pathogenesis of periodontitis. In contrast, A. actinomycetemcomitans did not affect the levels of antimicrobial factors in activated neutrophils and induced NET formation, ROS production, and secretion of MMP-8 and -9 in neutrophils alone, which might contribute to tissue destruction and disease progression. In summary, neutrophil responses to biofilms were species-specific and might support either maintenance of oral health or pathogenesis of periodontitis depending on the species.

摘要

口服先天免疫是由中性粒细胞引起的。尚不清楚它们针对不同生物膜的主要抗微生物机制可能如何促进口腔中的平衡或失调。我们调查了共生（链球菌）和致病性（牙龈卟啉单胞菌或集合放线菌放线菌）生物物种诱导或抑制嗜中性粒细胞的选定抗菌机制的能力。口头链球菌诱导中性粒细胞胞外陷阱（NETs）的形成，活性氧（ROS）的产生以及基质金属蛋白酶（MMP）8和9的分泌。但是，这些反应在PMA激活的中性粒细胞中有所减少，表明存在类似平衡的中性粒细胞反应，这可能对维持口腔健康很重要。牙龈卟啉单胞菌通常诱导ROS。在活化的嗜中性粒细胞中可检测到NET形成的减少和MMP分泌的显着降低，这突出了牙龈卟啉单胞菌的溶核和蛋白水解活性，这可能支持细菌定植和牙周炎的发病机理。相反，放线放线杆菌并不影响活化的中性粒细胞中的抗菌因子水平以及诱导的NET形成，ROS的产生以及仅中性粒细胞中MMP-8和-9的分泌，这可能有助于组织破坏和疾病进展。总之，中性粒细胞对生物膜的反应是特定物种的，视物种而定，可能支持维持口腔健康或牙周炎的发病机制。